There are three major aspects of the proposed Biotechnology Research Resource. First, the completion, programming and utilization of a new computing machine (Molecular Mechanics Computing Machine, MMCM) specifically designed to carry out the calculations involved in theoretical approaches to protein structure and function. The new system, which is currently being constructed, will provide computing power which is between 500 and 1,000 times greater than a VAX 11/780, the computer most commonly used for this work. It will be significantly faster than any of the super-computers now available or anticipated in the near future. However, it is very specific for problems in which most of the computing time is spent in determining the forces on each of many atoms which interact with pairwise central forces. These force calculations are to be carried out on a new hard-wired processor which we call FASTRUN and the calculation of the atomic displacement will be done on a commercial array processor. After the first year or so of the proposed grant when the system is functioning it will be available for collaborative and service use. The system will be used to study the interactions of enzymes and substrates, receptors and hormones and drugs designed as inhibitors of overactive proteins. The second major activity of the facility is the further development and use of an Automatic Nerve Tracing system for the 3-D reconstruction of portions of the neuropil of the brains of small mammals and simple invertebrates. New applications of the progress in computer science and image analysis will be applied to the problem and the system will be specifically designed to handle the EM images produced in various collaborative projects. The scientific problems are primarily those related to developmental neurobiology and the factors which influence the normal growth and connectivity pattern of brains. The third aspect of the work of the facility would involve the further development and use of our CARTOS (Computer Aided Reconstruction from Serial Sections) LOANER systems. These systems provide equipment and programs for tracing neurons in 3-D which can be used by investigators who are not located in the New York area. The LOANERS would be upgraded to provide for partial automation, both for EM work and work directly on light microscopes. One very important new collaborative project which will use the LOANERs is one in which a 3-D rat brain atlas will be maintained in the computer and programs will be written to allow neurobiologists working on neural-peptide localization to enter data directly into a 3-D data base and relate the new data to the atlas and other peptide localizations.